Impaired Antiviral and Type 3 Immune Responses in Crush Injury Patients With Earthquake-Related Trauma

Infections are frequent in critically ill patients with earthquake-associated crush injury (CI) and contribute to poor outcomes, yet the immune pathways underlying posttrauma susceptibility remain poorly defined. We investigated longitudinal changes in damage-associated molecular pattern (DAMP)/PAMP sensing and downstream inflammatory programs in CI patients requiring intensive care.

Nineteen CI patients admitted to the ICU after the February 6, 2023 Kahramanmaraş earthquake and 18 age- and sex-matched healthy controls were enrolled. Peripheral blood was collected on hospital days 7 and 21. DAMP/PAMP receptor expression was assessed by flow cytometry and RT-qPCR, and pathway activation was evaluated by phospho-flow (pSTING, pIRF3, pNF-κB, and p-cJun) in gated lymphocytes and monocytes. Plasma cytokines/alarmins and select DAMPs were quantified by multiplex enzyme-linked immunosorbent assay (ELISA)/assays.

CI patients demonstrated broad remodeling of nucleic acid-sensing programs, including reduced expression of TLR7, STING, and IRF7, with a discordant signaling pattern characterized by increased IRF3 phosphorylation, transiently reduced pSTING, and sustained reduction of p-cJun, while NF-κB activation remained comparatively stable. In plasma, IL-33 and IFN-α2 were reduced on Day 7, and type 3 immunity-associated cytokines IL-23 and IL-17A were significantly decreased by Day 21, consistent with impaired antimicrobial barrier-supporting responses. Circulating DAMPs were dynamically altered, with increased S100A9 and HMGB1 and decreased ATP following injury.

Earthquake-associated CI is associated with dynamic DAMP release and dysregulated innate sensing accompanied by suppression of antiviral and type 3 immune cytokine programs. These immune alterations may contribute to heightened vulnerability to secondary infections in critically ill CI patients.